Real-world efficacy and safety of pomalidomide-rituximab-based combination therapy in newly diagnosed extranodal diffuse large B-cell lymphoma

Abstract Introduction The R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone) has been established as the standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) in clinical practice. Approximately 30% to 40% of patients still experience relapsed or refractory disease following initial treatment with this regimen. Extranodal involvement of DLBCL often presents as highly invasive. Pomalidomide, a third-generation immunomodulatory agent, exhibits more potent immunomodulatory effects compared to lenalidomide. However, little is known about the real-world survival benefits and safety of pomalidomide-rituximab combination therapy in newly diagnosed adult extranodal DLBCL. Methods Eligible DLBCL patients with extranodal involvement (aged ≥18 years) were enrolled and analyzed at the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital. They received a pomalidomide-rituximab-based combination therapy as first-line treatment. Baseline characteristics, toxicities, and outcomes were collected through retrospective chart review. Efficacy assessment included overall response rate (ORR), complete response (CR), and partial response (PR), which were selected as the primary endpoints for this report. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results Fourteen patients with extranodal involvement suitable for efficacy evaluation were analyzed in this study. The involved sites included the gastrointestinal tract (n = 4), bone/bone marrow (n = 4), oropharyngeal region (n = 4), skin (n = 2), central nervous system (n = 1), testes (n = 1), and posterior eyeball (n = 1). Notably, half of the patients (7/14, 50%) exhibited involvement of ≥2 extranodal sites. Ten patients (71.4%) were male. Eleven patients (78.6%) were over 60 years old. 64.3% (9/14) of the patients were classified as Lugano Stage III-IV, and 42.8% (6/14) had an IPI (International Prognostic Index) of ≥3. 21.4% (3/14) of the patients were of GCB (germinal center B-cell) type, and 78.6% (11/14) were of non-GCB type. Patients with large masses accounted for 21.4%. CD5+ patients made up 57.1%. One patient exhibited p53 expression greater than 50%. Pomalidomide-rituximab was combined with CHOP-like regimens (n = 10), bendamustine (n = 1), brentuximab vedotin (n = 1), or BTK inhibitors (n = 2). The median number of treatment cycles administered was 4 (range, 2-8). The ORR was 92.9% (13/14), with a CR rate of 64.3% (n = 9), a PR rate of 28.5% (n = 4), and a progressive disease (PD) rate of 7.1% (n = 1). Among patients who completed four treatment cycles, the CR rate was 77.8% (7/9). CR was numerically lower in the GCB vs. non-GCB subtype (33.3% vs. 72.7%, P0.05), IPI 3-5 vs. IPI 1-2 (50% vs. 75%, P0.05), 60 years vs. ≤60 years (63.6% vs. 66.7%, P0.05), CD5- vs. CD5+ (50% vs.75%, P0.05) and patients with involvement of ≥2 extranodal sites vs. less than2 (57.1% vs. 71.4%, P0.05). Similarly, ORR was numerically lower in GCB vs. non-GCB subtype (66.7% vs. 100%, P0.05), IPI 3-5 vs.IPI 1-2 (83.3% vs. 100%, P 0.05), 60 years vs. ≤60 years (90.9% vs.100%, P 0.05), CD5- vs. CD5+ (83.3% vs.100%, P 0.05) and those with involvement of ≥2 extranodal site vs. less than2 (85.7% vs. 100%, P 0.05). The median follow-up duration was 6.74 months, with a cutoff date of July 23, 2025. The median time to response was 1.53 ± 0.55 months. The median time to achieve CR was 2.58 ± 0.63 months; median PFS and OS have not been reached. One patient died from Hemophagocytic lymphohistiocytosis. Continued follow-up will enable us to analyze survival differences across various subgroups. Regarding safety profiles, grade 3-4 hematological adverse effects (AEs) included thrombocytopenia (7.1%), anemia (14.2%), and neutropenia (71.4%). Grade 3-4 non-hematological AEs occurred in four patients, including one with hyponatremia and three with infections. Conclusion This real-world analysis demonstrated that the pomalidomide-rituximab-based combination therapy had promising efficacy, with a high ORR of 92.9%, in treatment-naïve DLBCL patients with extranodal disease, and exhibited acceptable hematological toxicity.